Maternal serum and placental metabolomes in association with prenatal exposure to per- and polyfluoroalkyl substances and their relevance to child neurodevelopment in an ASD-enriched cohort.

Scientists studied whether certain chemicals called PFAS (found in everyday products like non-stick cookware) during pregnancy might affect a child's brain development and autism risk. They looked at 172 mothers and children, measuring chemicals in the mother's blood and checking how they affected the body's chemistry. While they found the chemicals did change some aspects of the mother's body chemistry, they couldn't find a clear link to whether children developed autism or other developmental differences.

This study investigated whether prenatal exposure to per- and polyfluoroalkyl substances (PFAS) affects maternal metabolism and subsequently influences autism risk in children. Researchers analyzed 172 mother-child pairs from the MARBLES cohort, measuring PFAS in maternal blood and metabolites in both maternal serum and placental tissue. Children were assessed at age three for autism spectrum disorder (ASD), typical development, or non-typical development. While the study found associations between certain PFAS exposures and maternal metabolic changes, no clear connections were established between these metabolic alterations and child neurodevelopmental outcomes.

The findings suggest that gene-environment interactions may be important factors in understanding neurodevelopmental outcomes related to prenatal chemical exposures.

While prenatal PFAS exposure appears to alter maternal metabolism, the clinical significance for autism risk remains unclear. Findings suggest complex gene-environment interactions may be more important than direct metabolic pathways. Further research needed before clinical recommendations can be made.

Study design unclear from abstract. Relatively small sample size (172 pairs) may limit statistical power. Multiple comparison corrections applied suggest risk of type II error. Gene-environment interactions not directly measured but suggested as important confounding factors.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to altered neurodevelopment in children, but the contribution of maternal metabolic disruption to this relationship remains unclear. We investigated associations between prenatal PFAS exposure, maternal metabolism, and child neurodevelopment. We analyzed 172 mother-child pairs from the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) cohort. Nine PFAS were measured in maternal serum collected during pregnancy.

Metabolites were quantified in third-trimester serum and placental tissue using proton nuclear magnetic resonance (H-NMR) spectroscopy. At age three, children were clinically classified as having autism spectrum disorder (ASD), typical development (TD), or non-typical development (non-TD), the latter including children with atypical developmental features who do not meet the criteria for ASD. Multiple linear regression assessed associations between individual PFAS and metabolites, and quantile-based g-computation evaluated PFAS mixture effects. Principal component analysis (PCA) summarized metabolomic profiles.

One-way analysis of covariance (ANCOVA) and multinomial logistic regression examined associations between metabolites and child neurodevelopment. Correlation network analysis explored relationships among PFAS, serum, and placental metabolites. After multiple comparison correction, perfluorooctane sulfonate (PFOS) was significantly associated with serum 2-hydroxybutyrate (q < 0.10). Higher perfluorooctanoate (PFOA), PFOS, and PFAS mixture levels were associated with lower serum PC-2 scores.

Higher serum PC-3 score, reflecting mitochondrial dysfunction, was associated with increased non-TD risk. Network analysis identified 2-hydroxybutyrate as a key serum metabolite potentially linked to PFAS and placental amino acids. Prenatal PFAS exposure was associated with maternal metabolic alterations; however, no clear linkage to child neurodevelopment were observed. These findings suggest the need to consider gene-environment interactions in studies of neurodevelopmental outcomes.